Consequences of ubiquitin E2 enzyme (E2-25K) sumoylation

泛素和SUMO(小泛素相关修饰物)的翻译后修饰是大多数细胞通路中必不可少的蛋白质调节因子。泛素和相扑本身都是小蛋白，依靠严格调控的酶级联反应可逆地附着在底物上。这涉及修饰物特异性的E1激活、E2结合和E3连接酶用于结合以及修饰物特异性去结合的特定酶的顺序作用。调节主要在E3连接和去结合酶水平上进行，因为这些成分确保底物特异性。我们的工作旨在深入了解E2酶调控的后果，预计这将对所有下游事件、合作的E3连接酶及其底物产生广泛的影响。在这项拟议的研究中，我们将研究通过总甲基化调节泛素结合酶E2-25K的生物学后果。我们最新的生化发现表明，在SUMO化时，E2-25K会转换其对E3连接酶的偏好。我们现在的目标是通过调查整体表型和新发现的底物来研究E2-25K相加在细胞和小鼠模型中的后果。

Posttranslational modifications with ubiquitin and SUMO (small ubiquitin related modifier) are essential protein regulators involved in most cellular pathways. Ubiquitin and SUMO, themselves small proteins, are reversibly attached to their substrates depending on a tightly regulated enzymatic cascade. This involves the sequential action of a modifier specific E1 activating, E2 conjugating and E3 ligating enzyme for conjugation and specific enzymes for modifier specific deconjugation. Regulation is mainly performed at the level of E3 ligating and deconjugating enzymes, since these components ensure substrate specificity. Our work aims to gain insights into the consequences of E2 enzyme regulation which is expected to have widespread consequences on all downstream events, the cooperating E3 ligases and their substrates. In the proposed study we will investigate the biological consequences of regulating the ubiquitin conjugating enzyme E2-25K via sumoylation. Our recent biochemical findings indicated that upon sumoylation E2-25K switches its preference for E3 ligases. We now aim to study the consequences of E2-25K sumoylation in cell and mouse models by investigating the overall phenotype and also newly identified substrates.